WO2003044000A1 - Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1 - Google Patents

Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1 Download PDF

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Publication number
WO2003044000A1
WO2003044000A1 PCT/SE2002/002139 SE0202139W WO03044000A1 WO 2003044000 A1 WO2003044000 A1 WO 2003044000A1 SE 0202139 W SE0202139 W SE 0202139W WO 03044000 A1 WO03044000 A1 WO 03044000A1
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Prior art keywords
thiadiazol
chloro
methyl
amino
sulfonyl
Prior art date
Application number
PCT/SE2002/002139
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English (en)
French (fr)
Inventor
Meredith Williams
Guido Kurz
Marianne Nilsson
Jerk VALLGÅRDA
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Biovitrum Ab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biovitrum Ab filed Critical Biovitrum Ab
Priority to AU2002353717A priority Critical patent/AU2002353717B2/en
Priority to JP2003545637A priority patent/JP2005509676A/ja
Priority to EP02789089A priority patent/EP1461327A1/en
Priority to YUP-442/04A priority patent/RS44204A/sr
Priority to CA002466491A priority patent/CA2466491A1/en
Priority to MXPA04004842A priority patent/MXPA04004842A/es
Priority to IL16063002A priority patent/IL160630A0/xx
Priority to BR0214342-9A priority patent/BR0214342A/pt
Priority to EA200400708A priority patent/EA200400708A1/ru
Publication of WO2003044000A1 publication Critical patent/WO2003044000A1/en
Priority to NO20042161A priority patent/NO20042161L/no

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/433—Thidiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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    • A61P27/06—Antiglaucoma agents or miotics
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    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C07D285/135—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/36—Nitrogen atoms
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • Adrenalectomy attenuates the effect of fasting to increase both food intake and hypothalamic neuropeptide Y expression. This supports the role of glucocorticoids in promoting food intake and suggests that inhibition of 11 ⁇ HSDl in the brain might increase satiety and therefore reduce food intake (Woods, S.C et al. (1998) Science, 280: 1378-1383).
  • R 5 is acetyl, benzoyl, benzyl, ethyl, 2-fluoroethyl, 2-furylcarbonyl, hydrogen, isobutyryl, isopropyl, methyl, 2-carbomethoxyphenyl, methylsulfonyl, phenyl, n- propionyl, 3-pyridinyl, 2,2,2-trifluoroethyl;
  • R 3 and R 4 are each independently selected from ethyl, hydrogen or form together with the N-atom to which they are attached mo ⁇ holinyl;
  • R 5 O wherein R 5 is acetyl, benzoyl, benzyl, 2-fluoroethyl, 2-furylcarbonyl, hydrogen, isobutyryl, isopropyl, 2-carbomethoxyphenyl, methylsulfonyl, phenyl, n-propionyl, 3- pyridinyl, 2,2,2-trifluoroethyl.
  • C ⁇ - 6 -acyl in the compound of formula (I) according to the present application may be saturated or unsaturated and is preferably C ⁇ - 4 -acyl.
  • exemplary acyl groups include formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, butenoyl (e.g. 3-butenoyl), hexenoyl (e.g. 5-hexenoyl).
  • C ⁇ . 6 -acyl all subgroups thereof are contemplated such as C ⁇ . 5 -acyl, C ⁇ _ 4 -acyl, C ⁇ _ 3 -acyl, C ⁇ .
  • compositions according to the present invention may be in the form of tablets, capsules, powders, granules, lozenges, liquid or gel preparations, such as oral, topical or sterile parenteral solutions or suspensions.
  • Tablets and capsules for oral administration may be in unit dose presentation form and may contain conventional excipients such as binding agents, for example syrup, acacia, gelatin, sorbitol, traganath or polyvinyl-pyrrolidone; fillers e.g. lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine; tabletting lubricant e.g.
  • Oral liquid preparations may be in the form of e.g. aqueous or oily suspensions, solutions, emulsions, syrups or elixirs or may be presented as a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, e.g. sorbitol, syrup, methyl cellulose, glucose syrup, gelatin hydrogenated edible fats; emulsifying agents e.g.
  • the calculation of the Kj values for the inhibitors was performed by use of Activity Base.
  • the IC 5 o is measured experimentally in an assay wherein the decrease of the turnover of cortisone to cortisol is dependent on the inhibition potential of each substance.
  • the Ki values of the compounds of the present invention for the 11- ⁇ -HSDl enzyme lie typically between about 10 nM and about 10 ⁇ M.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Endocrinology (AREA)
  • Virology (AREA)
  • Hospice & Palliative Care (AREA)
  • Emergency Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
PCT/SE2002/002139 2001-11-22 2002-11-22 Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1 WO2003044000A1 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
AU2002353717A AU2002353717B2 (en) 2001-11-22 2002-11-22 Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
JP2003545637A JP2005509676A (ja) 2001-11-22 2002-11-22 １１−ベータ−ヒドロキシステロイドデヒドロゲナーゼ１型のインヒビター
EP02789089A EP1461327A1 (en) 2001-11-22 2002-11-22 Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
YUP-442/04A RS44204A (en) 2001-11-22 2002-11-22 Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
CA002466491A CA2466491A1 (en) 2001-11-22 2002-11-22 Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
MXPA04004842A MXPA04004842A (es) 2001-11-22 2002-11-22 Inhibidores de 11-(-hidroxiesteroide deshidrogenasa de tipo 1.
IL16063002A IL160630A0 (en) 2001-11-22 2002-11-22 Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
BR0214342-9A BR0214342A (pt) 2001-11-22 2002-11-22 Inibidores de 11 - beta - hidroxi esteróide desidrogenase tipo 1
EA200400708A EA200400708A1 (ru) 2001-11-22 2002-11-22 Ингибиторы 11-бета-гидроксистероиддегидрогеназы типа 1
NO20042161A NO20042161L (no) 2001-11-22 2004-05-25 Inhibitorer av 11-beta-hydroksysteroid dehydrogenase type 1

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
SE0103913-0 2001-11-22
SE0103913 2001-11-22
SE0104051-8 2001-11-30
SE0104051 2001-11-30
US34846802P 2002-01-14 2002-01-14
US60/348,468 2002-01-14

Publications (1)

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WO2003044000A1 true WO2003044000A1 (en) 2003-05-30

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PCT/SE2002/002139 WO2003044000A1 (en) 2001-11-22 2002-11-22 Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1

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EP (1) EP1461327A1 (pt)
JP (1) JP2005509676A (pt)
KR (1) KR20050044578A (pt)
CN (1) CN1649855A (pt)
AU (1) AU2002353717B2 (pt)
BR (1) BR0214342A (pt)
CA (1) CA2466491A1 (pt)
IL (1) IL160630A0 (pt)
MX (1) MXPA04004842A (pt)
NO (1) NO20042161L (pt)
PL (1) PL370447A1 (pt)
WO (1) WO2003044000A1 (pt)

Cited By (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004103980A1 (en) * 2003-05-21 2004-12-02 Biovitrum Ab Inhibitors of 11-beta-hydroxy steroid dehydrogenase type i
WO2004113310A1 (en) * 2003-06-25 2004-12-29 Biovitrum Ab Use of an inhibitor of 11-b-hydroxysteroid dehydrogenase type 1 compounds for promoting wound healing
US6849636B2 (en) 2002-12-20 2005-02-01 Merck & Co., Inc. Triazole derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1
WO2005042513A1 (en) * 2003-10-23 2005-05-12 Sterix Limited Phenyl carboxamide and sulfonamide derivatives for use as 11-beta-hydroxysteroid dehydrogenase
WO2005103023A1 (en) * 2004-04-20 2005-11-03 Sterix Limited Phenylsulfonamide derivatives for use as 11-beta-hydroxysteroid dehydrogenase inhibitors
WO2006048331A1 (en) * 2004-11-08 2006-05-11 Evotec Ag 11β-HSD1 INHIBITORS
WO2006050908A1 (en) * 2004-11-08 2006-05-18 Evotec Ag Inhibitors of 11βετα-hydroxy steroid dehydrogenase type 1 (11beta-hsd1)
US7074788B2 (en) 2001-11-22 2006-07-11 Biovitrum Ab Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
US7173030B2 (en) 2003-05-21 2007-02-06 Biovitrum Ab Inhibitors of 11-β-hydroxy steroid dehydrogenase type 1
WO2007025892A1 (en) 2005-08-31 2007-03-08 F. Hoffmann-La Roche Ag 11-beta-hydroxysteroid dehydrogenase-1-inhibitor-diabetes-type 2-1
US7230020B2 (en) 2003-10-23 2007-06-12 Sterix Limited 11β-hydroxysteroid dehydrogenase inhibitors
US7253196B2 (en) 2004-05-24 2007-08-07 Amgen, Inc. Inhibitors of 11-β-hydroxy steroid dehydrogenase type 1
WO2007128761A2 (de) 2006-05-04 2007-11-15 Boehringer Ingelheim International Gmbh Verwendungen von dpp iv inhibitoren
WO2008017381A1 (de) 2006-08-08 2008-02-14 Sanofi-Aventis Arylaminoaryl-alkyl-substituierte imidazolidin-2,4-dione, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und ihre verwendung
US7345058B2 (en) 2005-04-05 2008-03-18 Hoffmann-La Roche Inc. Pyrazoles
JP2008515826A (ja) * 2004-10-04 2008-05-15 エフ．ホフマン−ラ ロシュ アーゲー 糖尿病のための１１−β阻害剤としてのアルキルピリジン
DE102007005045A1 (de) 2007-01-26 2008-08-07 Sanofi-Aventis Phenothiazin Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
WO2009021740A2 (de) 2007-08-15 2009-02-19 Sanofis-Aventis Substituierte tetrahydronaphthaline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
EP2036548A1 (en) 2003-09-22 2009-03-18 onepharm Research & Development GmbH Prevention and treatment of inflammation-induced and/or immune-mediated bone loss
US7632838B2 (en) 2006-02-07 2009-12-15 Wyeth 11-beta HSD1 inhibitors
US7645773B2 (en) 2006-01-18 2010-01-12 Hoffmann-La Roche Inc. Thiazoles as inhibitors of 11β-hydroxysteroid dehydrogenase
WO2010003624A2 (en) 2008-07-09 2010-01-14 Sanofi-Aventis Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof
WO2010068601A1 (en) 2008-12-08 2010-06-17 Sanofi-Aventis A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof
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